• J. Obstet. Gynaecol. Res. · Mar 2018

    Progesterone inhibited endoplasmic reticulum stress associated apoptosis induced by interleukin-1β via the GRP78/PERK/CHOP pathway in BeWo cells.

    • Ling Liu, Yan Zhang, Yankui Wang, Wei Peng, Ning Zhang, and Yuanhua Ye.
    • Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, China.
    • J. Obstet. Gynaecol. Res. 2018 Mar 1; 44 (3): 463-473.

    AimPre-eclampsia (PE) is a pregnancy complication characterized by new onset maternal hypertension and proteinuria. Its underlying mechanisms are unclear. This study investigated the relationship between progesterone and endoplasmic reticulum stress (ERS) associated apoptosis induced by interleukin (IL)-1β via the glucose regulated protein 78 (GRP78)/protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C/EBP-homologous protein (CHOP) pathway in BeWo cells.MethodsVenous blood and placental tissues were collected from PE patients, normal pregnancy and preterm delivery cases, respectively. Progesterone serum levels were detected by enzyme-linked immunosorbent assay and ERS-related protein expression in placentas was examined by immunohistochemistry, reverse transcriptase-polymerase chain reaction and Western blot. BeWo cells were stimulated by IL-1β to induce ERS associated apoptosis in vitro. The apoptotic rate was measured by flow cytometry. The mechanism of progesterone acting on IL-1β induced ERS associated apoptosis was investigated by reverse transcriptase-polymerase chain reaction, Western blot and PERK small interfering RNA, with RU486 used as a receptor inhibitor.ResultsPE patients exhibited decreased serum levels of progesterone and activated ERS and increased ERS-related protein expression. IL-1β could induce ERS and associated cell apoptosis by activating the GRP78/PERK/CHOP signal pathway, which could be inhibited by progesterone. PERK could be upregulated and phosphorylation activated in ERS. The protective effects of progesterone could be attenuated by RU486.ConclusionIL-1β could induce ERS associated cell apoptosis by activating the GRP78/PERK/CHOP signal pathway in BeWo cells and may play an important role in PE occurrence. Progesterone levels were decreased in patients with PE and seemed to have a protective effect by inhibiting ERS associated cell apoptosis.© 2017 Japan Society of Obstetrics and Gynecology.

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